Articular cartilage has limited ability to regenerate and repair [1,2]. Current therapies do not restore a normal hyaline cartilage [3]. Osteoarthritis (OA) affects 27 million adults in the United States and the number is anticipated to rise to 67 million by 2030 [4]. Knee and hip replacements cost almost $42.3 billion in 2009 [4]. With OA beginning at about age 45 and early onset OA developing within 10 years of a major joint injury [5], there is a growing need for an effective treatment to repair articular cartilage.
Conventional approaches in tissue engineering and regenerative medicine utilize cells and/or growth factors in combination with biomaterial scaffolds to repair tissues. Mesenchymal stem cells (MSCs) derived from adult bone marrow are of great interest as a cell type due to their proliferative capacity and their ability to differentiate into multiple lineages including bone and cartilage cells [1,6]. These cells are also being investigated in clinical trials for cartilage repair [7] using liver and pancreas tissues.
Different approaches have been used to stimulate chondrogenesis and bone growth such as the use of transforming growth factor beta (TGF-β), bone morphogenetic protein (BMP) [8,9] and insulin and insulin-like growth factors (IGF) [10]. IGF-1 is involved in MSC chondrogenesis by stimulating proliferation, regulating apoptosis and inducing differentiation [10]. Insulin is structurally similar to IGF-1 whereby it can bind to the IGF-1 receptor and stimulate extracellular matrix (ECM) production [11].
Previous studies have found that systemic insulin treatment increased cell proliferation, soft callus formation/chondrogenesis, biomechanical properties and callus bone content in diabetes mellitus rats [12]. Furthermore, local administration of insulin has been found to improve healing and bone regeneration in animal models [13,14].
However, insulin is difficult to deliver locally due to its high molecular weight (51 amino acids and 5808 Da molecular weight (MW)) and stability; insulin goes through hydrolysis/degradation or intermolecular transformation during storage and use [15]. Moreover, increasing the insulin level in normal patients is not an option because of the risk of hypoglycemia. Therefore, insulin-mimetics have been sought.
In addition, the general approach to the use of tissue engineering in the repair and/or regeneration of tissue is to combine cells and/or biological factors with a biomaterial that acts as a scaffold for tissue development. The cells should be capable of propagating on a scaffold and acquiring the requisite organization and function to produce a properly functioning tissue, cartilage, bone, or both cartilage and bone.
Electrical stimulation is known to promote cellular growth. However there is a problem with electrical stimulus needing external power sources or batteries that can cause negative patient implications, and is cumbersome for the user.
Thus there still remains a need for innovative technologies for tissue engineering of inherently complex tissues, and in particular, musculoskeletal connective tissue such as cartilage and/or bone without the above drawbacks. Furthermore there also remains a need in the art for compositions and methods that are capable of inducing bone and/or cartilage growth and repair.